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Direct visualization of antigen-specific T cells: HTLV-1 Tax11–19- specific CD8+T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patient...
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 95, 1998, 13, S. 7568-7573 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11–19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2–Ig complex to directly visualize HTLV-1 Tax11–19-specific T cells from peripheral blood and cerebrospinal fluid without<jats:italic>in vitro</jats:italic>stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8<jats:sup><jats:italic>+</jats:italic></jats:sup>lymphocytes specific for the HTLV-1 Tax11–19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11–19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11–19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11–19-specific CD8<jats:sup><jats:italic>+</jats:italic></jats:sup>T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-α and γ-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11–19-specific CD8<jats:sup><jats:italic>+</jats:italic></jats:sup>T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.</jats:p> |
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| Umfang: | 7568-7573 |
| ISSN: |
0027-8424
1091-6490 |
| DOI: | 10.1073/pnas.95.13.7568 |